Patrick Trucchio

Patrick Trucchio inquired about the specific elements of ARO-MAPT's healthy volunteer data (safety, CSF tau knockdown, biomarkers) that would build confidence, what to look for in patient data, and how this would validate the CNS targeting platform.

Answer

James Hamilton, Chief Medical Officer and Head of R&D, expressed confidence from consistent preclinical monkey data showing deep brain knockdown across multiple targets. He highlighted safety and CSF knockdown as key confidence-building data in healthy volunteers. For patient cohorts, he mentioned measuring phospho-tau varieties in blood and CSF, and eventually tau PET signals, as important indicators.

Patrick Trucchio asked about key confidence-building elements in the upcoming ARO-MAPT healthy volunteer data, such as safety, CSF tau knockdown, or biomarkers. He also inquired about critical patient data points to watch and how these results would validate the CNS targeting platform and its future development.

Answer

James Hamilton, Chief Medical Officer and Head of R&D, highlighted that preclinical monkey data across multiple CNS targets consistently showed deep brain knockdown, boosting confidence in the platform. For ARO-MAPT, he stated that safety and CSF tau knockdown in healthy volunteers would be key, followed by phospho-tau measurements in blood/CSF and tau PET signals in patient cohorts as crucial indicators of success.

Patrick Trucchio inquired about payer access for FCS, potential coverage differentiation for SHTG patients, and the expected pricing relationship between the FCS and SHTG indications.

Answer

CEO Christopher Anzalone addressed pricing, stating that while they are not ready to provide a specific price for the SHTG indication, they would expect it to be priced lower than for the rare disease FCS indication.

Patrick Trucchio of H.C. Wainwright & Co. asked about the strategic positioning of the ARO-C3 and ARO-CFB programs and whether they are considered core assets or potential partnering opportunities.

Answer

An executive stated the company is open to partnerships for ARO-C3 and Factor B if the right economics can be found. Chief Medical Officer, Dr. James Hamilton, added that ARO-C3 data in IgAN shows a competitive 41% reduction in proteinuria, which, combined with infrequent dosing, could be advantageous.

Patrick Trucchio asked for a review of plozasiran's competitive positioning against olozarsen in both FCS and SHTG. He also inquired about attractive targets and disease areas for the company's adipose tissue-targeting platform.

Answer

Andy Davis, Head of Global Cardiometabolic Franchise, highlighted plozasiran's differentiation through deeper triglyceride reduction, achieving risk thresholds, a statistically significant reduction in pancreatitis risk, and convenient quarterly dosing. Dr. Bruce Given added that the SHTG market will be expanded by both companies. Dr. James Hamilton noted obesity, type 2 diabetes, and lipodystrophy as target indications for the adipose platform but did not disclose specific targets.

Patrick Trucchio of H.C. Wainwright & Co. asked about the citizen petition on benzethonium chloride, including the FDA response timeline and potential revenue impact. He also inquired about the FDA's view on real-world data for NRX-100 and the potential synergy between NRX-101 and TMS therapy.

Answer

CEO Jonathan Javitt explained the FDA has six months to respond to the petition, and a favorable outcome could give NRXP a substantial share of the $750M generic ketamine market. He stated that the large real-world dataset should strengthen the NRX-100 application and discussed a potential label expansion for NRX-101 to be used with TMS, citing a study showing it enhanced TMS efficacy.

Patrick Trucchio from H.C. Wainwright & Co. asked about the potential Phase 3 dosing and endpoint strategy for pemvidutide in NASH. He also inquired about the drug's prospective commercial positioning and key points of differentiation if Phase 3 results mirror the IMPACT trial's efficacy and tolerability profile.

Answer

Chief Medical Officer Dr. M. Scott Harris indicated the 2.4mg dose is attractive for Phase 3 and that various endpoint strategies are being considered for FDA discussion. CEO Dr. Vipin Garg highlighted the key commercial differentiators as the combination of direct liver action with weight loss, a class-leading safety profile, and the lack of need for dose titration.

Patrick Trucchio of H.C. Wainwright & Co. requested more details on the triple reader model for the IMPACT trial, the specific start date for the Phase III MASH trial, and how the MASH program would be sequenced with trials in other indications.

Answer

CMO Dr. Scott Harris detailed the 3-reader 'mode' approach and blinded rereads, designed to control the placebo effect, and confirmed a Phase III start is anticipated in Q1 2026 following a year-end end-of-Phase II meeting. CEO Dr. Vipin Garg added that the smaller proof-of-concept trials for new indications are running in parallel and can be sequenced easily without delaying the primary MASH Phase III program.

Patrick Trucchio of H.C. Wainwright & Co. asked for clarification on whether ChemTrak's growth was driven more by new patients or longer treatment durations, and inquired about the criteria for initiating the expansion cohort in the HIV program.

Answer

Ralph Torbay, EVP of Commercial, explained growth was driven by both, but primarily by increased market penetration, with duration of therapy providing a tailwind. David Berman, EVP of R&D, stated the HIV expansion would be triggered by demonstrating viral control beyond the initial 12-week protocol and identifying the right dose, building on exciting early signals.

Patrick Trucchio from H.C. Wainwright & Co. inquired if the HIV MAD data could suggest a combination strategy for M113V and whether the program might qualify for priority review or other accelerated development pathways.

Answer

David Berman, Head of R&D, confirmed that the platform is combinable and the ultimate goal is a finite dosing regimen allowing patients to stop all therapies. He stated that while regulatory incentives like priority review are a consideration for the future, it is too early to comment on them before generating more definitive data.

Asked for more details on the PRAME Phase III program, including the strategy for first-line treatment, the combination trial design, contribution of components, and the timing and potential read-through of ctDNA data.

Answer

David Berman explained the first-line strategy is supported by monotherapy activity and the principle that immunotherapies work better in earlier lines. The trial design (PRAME+nivo vs. nivo) inherently assesses the contribution of components. The primary endpoint is PFS, and ctDNA is an exploratory endpoint with data not expected until the trial is open.

Patrick Trucchio of H.C. Wainwright & Co. sought clarification on the U.S. regulatory filing strategy for HDV, the primary purpose of the ECLIPSE-3 head-to-head trial, and how the VIR-5525 study is designed to capture data in KRAS mutant tumors.

Answer

EVP & Chief Medical Officer Dr. Mark Eisner reiterated that the base case for U.S. filing is ECLIPSE-1 and -2, but using ECLIPSE-1 and SOLSTICE remains an option. He confirmed ECLIPSE-3 is primarily to support European payer negotiations by demonstrating superiority over bulevirtide. EVP of Oncology Dr. Mika Derynck explained that the VIR-5525 trial will enroll patients who have exhausted standard care, including KRAS inhibitors, and emphasized that the T-cell engager's mechanism is independent of downstream mutations like KRAS.

Patrick Trucchio asked a series of questions regarding the CHB program's functional cure rate targets, the regulatory submission plan for the HDV program, and the company's partnering strategy for both the CHB and preclinical PRO-XTEN programs.

Answer

Mark Eisner (Executive) confirmed that for CHB, the best responses were in patients with baseline surface antigen levels below 1,000. For HDV, he stated that data from ECLIPSE-1 and ECLIPSE-2 should be sufficient for a filing package under an accelerated approval pathway. Marianne De Backer (Executive) added that the preclinical PRO-XTEN strategy involves a mix of internal development for high-priority targets and partnerships for others.

Patrick Trucchio from H.C. Wainwright asked for any further learnings from the SOLSTICE HDV data that could inform the ECLIPSE program. He also inquired about the relative importance of reducing HB surface antigen in the HDV setting and how to think about this for the combination therapy versus monotherapy for long-term outcomes.

Answer

Dr. Mark Eisner, CMO, highlighted that learnings from the SOLSTICE trial about disease demographics have informed site and investigator selection for the ECLIPSE program to optimize Phase III. He emphasized the importance of the 3-log reduction in hepatitis B surface antigen seen with the combination therapy, stating it's critical for the delta virus life cycle. He expressed hope that this profound viral suppression will translate into better long-term outcomes for patients, such as less progression to cirrhosis.

Patrick Trucchio inquired about the expected differentiation of Vir's HDV combination therapy compared to bulevirtide. For the HBV program, he asked if the 20-30% functional cure targets apply to all-comers or a specific patient subset, and whether a Phase III trial might stratify patients by baseline S-antigen levels.

Answer

Dr. Mark Eisner, Chief Medical Officer, stated that Vir's HDV combo is expected to achieve much higher 'target not detected' rates than bulevirtide. He also expressed confidence in the response for patients switching from bulevirtide. For the HBV program, he deferred questions on patient stratification to the upcoming data presentation at the AASLD liver meeting.

Patrick Trucchio from H.C. Wainwright & Co. requested details on the trial design for the upcoming pitolisant HD Phase 3 studies and inquired about the commercial launch strategy for ZYN-two, including community engagement and expected market uptake.

Answer

Chief Medical & Scientific Officer Dr. Kumar Budur described the pitolisant HD trials as standard randomized, placebo-controlled studies. Regarding the ZYN-two launch, EVP & CCO Adam Zaeske highlighted the high awareness and receptivity expected from the close-knit Fragile X community. President & CEO Dr. Jeffrey Dayno added that engaging with rare disease communities is a core strength of Harmony.

Patrick Trucchio asked about the key drivers of the 2025 revenue guidance and for a preview of the upcoming Phase III trial designs for pitolisant HD, specifically if fatigue and sleep inertia would be powered endpoints.

Answer

CCO Adam Zaeske cited continued growth in patients on therapy as the primary driver for guidance. Dr. Kumar Budur, CMSO, confirmed the IH study design is set and the narcolepsy design will be shared later. He stated the goal is to eventually secure a fatigue indication for narcolepsy, supported by extensive ongoing research.

Luis, on behalf of Patrick Trucchio at H.C. Wainwright & Co., asked about potential differences in the regulatory approval path for AMT-130 in Europe versus the U.S. and about the patient population for the planned Phase II portion of the AMT-260 epilepsy study.

Answer

CEO Matt Kapusta stated that the company has not yet met with the EMA for AMT-130 but plans to do so after the three-year data is available. CMO Walid Abi-Saab noted it is premature to detail the AMT-260 Phase II design but suggested a natural progression would be to expand into patient populations with a higher unmet need, such as those with dominant and bilateral disease.

Patrick Trucchio asked for clarification on whether additional regulatory interactions are expected before the AMT-130 BLA filing and requested details on the three immunosuppression-related SAEs in Cohort 3.

Answer

CEO Matthew Kapusta stated that uniQure has had constructive interactions and will provide a full regulatory update later in the quarter. CMO Dr. Walid Abi-Saab detailed the three SAEs (mania, infection, fever) were related to the triple immunosuppression regimen, not AMT-130, and all resolved. He concluded that a short, 2-week course of corticosteroids is likely the optimal path forward.

Patrick Trucchio asked about the number of enrolled patients who previously discontinued sotatercept, the read-through and commercial implications of the open-label extension (OLE) data, the rationale for the doses in the PH-ILD study, and the implications of demonstrating a benefit on the underlying lung disease.

Answer

CFO & COO Bryan Giraudo noted very few sotatercept discontinuations (high single digits) were enrolled. CEO Faheem Hasnain and an executive, likely CCO Bob Smith, emphasized the OLE data's commercial importance, positioning seralutinib for earlier use due to its safety and potential for sustained improvement. Regarding PH-ILD, Mr. Hasnain explained the higher 120mg dose aims to deliver more drug to fibrotic lung tissue. An executive, likely CCO Bob Smith, added that a positive result on the FVC endpoint would be a major commercial differentiator, especially in the EU.

Speaking on behalf of Patrick Trucchio, a representative from H.C. Wainwright & Co. asked for more details on the new measles discovery program, including its clinical path, market potential, and how it would be prioritized given the company's cash position and new loan facility.

Answer

Marc Elia, Chairman, clarified that the measles program is an addition, not a pivot, and is funded within existing discovery budgets without being a significant incremental draw on cash. He emphasized that the move is about adding long-term optionality and value, consistent with the company's disciplined capital stewardship. He also noted potential national-level interest in such a program.

Asked about the regulatory authorization pathway for VYD2311, specifically if a single EUA could cover both treatment and prevention, whether this depends on titer threshold discussions, and when to expect the first titer data.

Answer

The company is actively considering the regulatory path for VYD2311 and believes the immunobridging concept could be extrapolated from prevention to treatment, potentially allowing for a streamlined path. They are confident in efficacy at relatively low titers based on past and recent data, aiming for broad, equitable protection rather than extremely high titers for a few. First-in-human data, including PK and titers, is currently being generated and will be discussed with the FDA.

Representing Patrick Trucchio of H.C. Wainwright, an analyst asked about the regulatory path for VYD2311, including whether separate trials would be needed for prevention and treatment, and the potential for an accelerated approval. A follow-up question concerned whether approval would depend on a specific titer threshold and the timing for the first titer data readout.

Answer

Chairman Marc Elia explained that these are active discussion topics with the FDA and that the immunobridging concept used for prevention is scientifically applicable to treatment. He emphasized the company's goal is to provide an 'appropriate' titer for broad, equitable protection, not necessarily the highest possible titer. Dr. Mark Wingertzahn, SVP of Clinical Development, concurred that the immunobridging data can be extrapolated. Management noted they are currently gathering the first-in-human safety and PK data for VYD2311.

The analyst inquired about the reimbursement strategy for the non-CMS half of the target population, the potential approval pathway and timeline for PEMGARDA as a treatment, and the potential impact of this label expansion on peak sales.

Answer

The company responded that their team is actively working on securing commercial reimbursement, which is a process that takes time. For the treatment EUA, the submission is described as 'imminent' (weeks, not months) and will leverage existing clinical data. They are excited about the opportunity but are not updating financial guidance or commenting on peak sales potential at this time.

Patrick Trucchio of H.C. Wainwright & Co. inquired about the reimbursement strategy for the patient population not covered by CMS codes, the potential timeline for a PEMGARDA treatment EUA, and its anticipated impact on peak sales.

Answer

Marc Elia, Chairman, indicated that the EUA submission for treatment was 'imminent,' suggesting a timeframe of weeks. He noted the submission leverages existing data and alignment with the FDA. Jeremy Gowler, Interim CEO, added that the company's national account team is actively working to secure commercial payer coverage for the non-CMS population and is encouraged by initial engagements.

Patrick Trucchio of H.C. Wainwright & Co. inquired about the registrational trial for HR+/HER2- metastatic breast cancer, including its potential design, primary endpoint, and regulatory feedback. He also asked about recent FDA interactions regarding the pancreatic cancer program, priorities for business development such as regional rights or co-development, and plans for exploring additional combination therapies.

Answer

Dr. Tom Heineman, Chief Medical Officer, confirmed that the company discussed the breast cancer study with the FDA and anticipates progression-free survival (PFS) will be the primary endpoint. For pancreatic cancer, he noted no recent FDA discussions but highlighted the existing Fast Track designation. Christophe Degois, VP of Business Development, added that the company is exploring both global and regional partnerships to maximize pelareorep's value, with breast and pancreatic cancer as top priorities. Dr. Heineman also explained that pelareorep shows synergy with checkpoint inhibitors, particularly in pancreatic cancer, which will be leveraged on an indication-by-indication basis.

Patrick Trucchio inquired about the potential trial design for the upcoming registrational study in HR+/HER2- metastatic breast cancer, including the primary endpoint and regulatory feedback. He also asked about recent FDA interactions regarding the pancreatic cancer program and potential registrational pathways, as well as business development priorities and plans for additional combination therapies.

Answer

Chief Medical Officer Dr. Tom Heineman confirmed that progression-free survival (PFS) is the anticipated primary endpoint for the breast cancer trial, based on prior FDA discussions. He noted no recent additional FDA meetings on the pancreatic cancer program but mentioned ongoing protocol development with GCAR. Dr. Heineman also affirmed that combination strategies with checkpoint inhibitors are being explored on an indication-by-indication basis. VP of Business Development Christophe DeGois added that the company is pursuing both global and regional partnerships to maximize the value of pelareorep, with breast and pancreatic cancer as top priorities.

Patrick Trucchio of H.C. Wainwright asked how to interpret the 52-week follow-up data for commercialization, if the pivotal program tracks concomitant medication use, and about the status of regulatory interactions for the PTSD program.

Answer

Dr. Steve Levine (CPO) emphasized that even 6-week durability would be a paradigm shift, with the 52-week data providing a strong signal. Dr. Guy Goodwin (CMO) confirmed that other medication use is tracked and adds a real-world element to the data. CEO Kabir Nath stated that while they will discuss PTSD plans with the FDA, they do not disclose specific feedback from regulatory interactions.

Patrick Trucchio asked for context on what constitutes a clinically meaningful MADRS improvement and for details on the psychological support model, including how it differs from past approaches and its implications for regulatory approval and commercial scale-up.

Answer

Chief Medical Officer Dr. Guy Goodwin referenced the approximate 13-point MADRS change seen in the Phase II study as a positive benchmark. He explained the current psychological support model is simplified and protocolized to isolate the drug's effect for the FDA. Chief Commercial Officer Lori Englebert added that launch requirements are expected to be similar to SPRAVATO's REMS, while Chief Patient Officer Dr. Steve Levin noted they are leveraging partner collaborations to inform real-world training.

Patrick Trucchio of H.C. Wainwright asked if both Phase III trials are still required for an NDA submission and if an FDA Advisory Committee (AdCom) is expected. He also inquired how the trial timeline changes might strengthen their position for a potential AdCom and how the COMP 005 data might read through to the COMP 006 trial.

Answer

Kabir Nath (Executive) confirmed that data from both trials are expected to be necessary for filing and that an AdCom is anticipated. An unnamed executive (Michael) added that protecting the blinding of the 006 study strengthens their regulatory position for an AdCom. He also noted that steps are being taken to prevent read-through from 005 to 006, such as not using overlapping trial sites.

Patrick Trucchio's representative, Luis Santos, inquired about the timeline for the Fabry program partnership, whether additional data is awaited, and the potential for a new partnership for the recently returned Hemophilia A program.

Answer

CEO Sandy Macrae explained that late-stage Fabry partnership discussions with several parties are ongoing, with a deal anticipated in Q2 2025, supported by strong data with a full readout expected soon. Regarding Hemophilia A, Macrae noted the program was near filing when returned by Pfizer, and Sangamo has already received inbound interest for a new partnership, with full data rights transferring from Pfizer.

Patrick Trucchio asked how the single ascending dose (SAD) data influenced the multiple ascending dose (MAD) study for VY-7523, how the study is designed for differentiation, and how Voyager will balance internal investment against business development with its current cash runway.

Answer

CMO Dr. Toby Ferguson said the favorable SAD data gave them confidence to push to higher doses in the MAD study to test for a clear tau PET signal. CFO Dr. Nathan Jorgensen emphasized the mid-2027 runway is a priority and would only be shortened for a compelling near-term asset. CEO Dr. Al Sandrock reiterated openness to various partnership structures to secure non-dilutive funding.

Patrick Trucchio asked about the appropriate tau PET burden for patient selection for VY7523, the advantages of the tau silencing gene therapy versus antibodies, the remaining steps for the 2026 IND filing for the gene therapy, and the advantages of Voyager's capsid platform.

Answer

CEO Dr. Alfred Sandrock stated that more data is needed to define a specific tau PET burden cutoff for patient selection. Chief Scientific Officer Dr. Todd Carter highlighted that the gene therapy approach could potentially reduce existing tau burden, not just slow accumulation, and offers a one-time IV dose with broad CNS delivery. Chief Medical Officer Dr. Toby Ferguson added that standard IND-enabling toxicology studies are the key next steps for the gene therapy program and noted the potential for a larger clinical effect size with a knockdown approach compared to anti-amyloid therapies.

Patrick Trucchio of H.C. Wainwright & Co. asked about potential read-throughs from the upcoming donanemab advisory committee for Voyager's Alzheimer's programs and for a comparison of the recent ASGCT tau reduction data with prior-generation capsids.

Answer

Executive Alfred Sandrock stated that while the donanemab adcomm is of interest, particularly regarding important outcome measures, it may have limited direct impact on their programs. Executive Todd Carter explained that the recent tau knockdown data in mice used a mouse-capable capsid to validate the payload's ability to reduce tau mRNA and protein, building proof-of-concept as they advance novel capsids for human studies.

Patrick Trucchio of H.C. Wainwright & Co. asked about key secondary endpoints, ongoing HEOR research, how Phase IIb learnings influenced Phase III powering, and how long-term durability is measured in Part B of the studies.

Answer

CEO Robert Barrow identified CGI (Clinical Global Impressions) as a key secondary endpoint and detailed HEOR research focused on GAD's economic burden. He explained the Phase III trials are conservatively powered for a 5-point improvement over placebo, despite seeing a ~8-point improvement in Phase IIb. For durability, Part B uses a 9-month extension to track time to relapse or re-treatment, noting historical precedent for GAD approvals often required only 2-12 weeks of data.

Patrick Trucchio asked about the expected read-through from the VOYAGE trial to the PANORAMA trial, what the company aims to learn from further regulatory discussions for the second MDD trial, and how long-term extension data could help address functional blinding concerns.

Answer

Executive Robert Barrow stated that they anticipate conducting two MDD studies and that regulatory discussions are to ensure full alignment on the second study's design. He expects the VOYAGE results to demonstrate consistency of response. He also reiterated that the lower dose in PANORAMA acts as a secondary control to confuse expectancy bias, building on Phase II data that already supports a true drug effect independent of functional unblinding.

Asked about the strategy for Zerlasiran's Phase III (solo vs. partner), the timing of FDA meetings relative to data releases, the reason for Mallinckrodt discontinuing SLN501, and the company's overall complement program strategy.

Answer

The company is moving 'full steam ahead' with Phase III planning for Zerlasiran and has the funding to advance it, but is also actively looking at partnerships. They will wait for the 48-week data before meeting with the FDA to help confirm the dosing strategy. Regarding SLN501, Mallinckrodt's decision was noted, and Silence had already reacquired the two preclinical complement assets they believed were the best fit. Their strategy for the complement program is a portfolio approach, focusing on their two in-house assets which they believe may offer a more competitive opportunity.

Patrick Trucchio of H.C. Wainwright & Co. asked which upcoming catalysts are most underappreciated, the ideal outcome for Compass's end-of-Phase II meeting, how the various TRD programs fit together, and details on the DMX-1002 dose selection and expected safety data.

Answer

CSO Dr. Srini Rao identified the GABA (GRX-917) and DMT (VLS-01) programs as potentially underappreciated. He stated the ideal outcome for Compass is FDA clearance for Phase III. He positioned the TRD assets as complementary, with COMP360 as an anchor, DMT as a 2nd-gen option, and R-ketamine and Salvinorin A as differentiated mechanisms. For DMX-1002, he said the key safety data will focus on characterizing cardiovascular effects.

Patrick Trucchio from H.C. Wainwright asked for the timeline for Phase I data, the translatability of animal data, potential clinical doses for CYB003, and whether the trial would be a combined Phase I/IIa design.

Answer

CEO Doug Drysdale projected initial PK data could be available within approximately six months of the trial's commencement in mid-2022, expressing high confidence in translating the consistent cross-species PK data to humans. He stated the dose would likely be half that of psilocybin and that a multi-dose cohort is being considered for Phase II. He also confirmed plans for a seamless Phase I/IIa study design by leveraging both U.S. and U.K. regulatory environments.